The penetration characteristics of piperacillin-tazobactam into cortical and cancellous bone tissues were investigated in 10 patients undergoing total hip replacement. The concentration ratios of piperacillin/tazobactam were 9.4 +/- 1.8 in cancellous bone tissue and 8.0 +/- 2.2 in cortical bone tissue, which were close to the 8:1 ratio of drugs administered. The mean ratios of drug concentrations in bone and plasma for cancellous and cortical tissue were 23 and 18%, respectively, for piperacillin and 26 and 22%, respectively, for tazobactam. The concentrations of tazobactam achieved are sufficient to exert anti-beta-lactamase activity and supportive of clinical trials involving bone and joint infections, including those caused by beta-lactamase-producing pathogens.